The electric field transmitted by electrodes placed on the scalp can unlock the ability of immunotherapy to glioblastoma, the deadliest form of brain cancer.
New research from USC shows that comparing this electric field therapy with immunotherapy and chemotherapy has expanded survival by 70% compared to previous therapies. This discovery offers special hope for patients with large tumors facing the most desolate prognosis – these patients have a lifespan of 13 months than expected and have the strongest immune response to treatment.
A new weapon against ruthless enemies
Glioblastoma strikes with devastating efficiency. According to the National Brain Tumor Association, the average survival time after diagnosis was only eight months. Even after receiving active treatments including surgery, radiation and chemotherapy, less than 15% of patients survived for five years.
The challenge partly lies in the location of glioblastoma. These tumors grow in the brain and are protected by the blood-brain barrier that usually blocks nerve tissue from harmful substances. Unfortunately, the same obstacles prevent many anti-cancer immune cells and treatments from reaching their goals.
“By using TTFIELDS of immunotherapy, we use the body to stimulate against cancer, which allows immunotherapy to have meaningful effects in ways that have never been possible,” said Dr. David David Tran, director of neurology at Keck Medicine.
How electric fields fight cancer
Tumor treatment fields (TTFields) represent a fundamentally different approach to cancer treatment. Instead of using drugs or radiation, the treatment directly transmits a low-intensity electric field into the tumor through electrodes placed on the patient’s scalp.
These alternating electric fields create chaos inside cancer cells. They push and pull the key cell structure in the direction of constant metastasis, making it almost impossible for tumor cells to successfully divide and reproduce. The patient wears a mesh electrode for approximately 18 hours a day and receives the exact frequency that calibrates their specific tumor location.
But TTFields not only destroy cancer cell division. The electric field attracts anti-tumor T cells (leukocytes that recognize and attack cancer) in the tumor area. When used in combination with immunotherapy, these T cells remain active longer and are enhanced by more effective anti-cancer cells.
Key research results:
- Overall survival rate increased by 70% in triple therapy combination
- Patients with inoperable tumors have 13 months longer than expected
- Only 7.5% of treatment-related side effects are severe
- Larger tumors have stronger immune response to treatment
- Electric fields specifically activate immune pathways in dendritic cells
Amazing advantages of inoperable tumors
Traditional beliefs show that removing as many tumors as possible can provide patients with the best chance of survival. But this study reveals something unexpected: The tumor is too big or dangerous to be surgically unsustainable in fact responding better to electric field treatment.
Seven patients with only biopsy tumors (meaning surgeons who can only take tissue samples instead of removing cancer) showed significant improvement. The almost complete reaction was achieved twice, the partial reaction was achieved twice, and the disease was maintained for a long time.
The team discovered why large tumors respond so much. The study’s immune monitoring shows that electric fields work by triggering what scientists call “in situ immunity,” which actually turns the tumor itself into a vaccine factory. Larger tumors provide more targets for this immune activation, resulting in a more robust anti-cancer response.
The molecular mechanism behind success
This study goes far beyond the range of measuring survival time. Using advanced technology, including single-cell RNA sequencing, the team tracks how treatments affect patients’ immune systems at molecular levels, an important detail missing in news reports.
They found that the electric field specifically activates the type I interferon pathway in dendritic cells, i.e., the immune cells that specify the general to command the human body’s anti-cancer power. This activation occurs within four weeks after the initiation of electric field therapy, even before the addition of immunotherapy to the treatment regimen.
The interferon pathway then triggers the activation and expansion of T cells, forming a group of anti-cancer cells. When immunotherapy is added, it persists and expands this immune response, leading researchers to call it an “adaptive alternative” to the T-cell population of increasingly effective cancer fighters.
A team campaign for cancer
Dr. Tran uses sports analogies to explain how the combination works: “Think of it as a team sport – immunotherapy sends players to attack tumors (offense), while TTFields weakens the ability to counterattack (defense). Just like in team sport, the best defense is a good offense.”
This team-work approach solves the fundamental problems of treating brain cancer. Immunotherapy drugs such as pembrolizumab have revolutionized the treatment of many cancers, but they largely failed glioblastoma. The brain’s immune properties environment, coupled with the ability of glioblasts to inhibit immune responses, makes these powerful drugs ineffective when used alone.
When the tumor strikes back
The study also reveals how glioblastoma adapts to evade treatment – far beyond typical research abstracts. When the researchers analyzed recurrent tumors in patients whose cancer finally recovered, they discovered a complex mechanism of drug resistance.
These tumors basically reconnect to the molecular defense. Although PD-1/PD-L1 immune checkpoints targeted by pembrolizumab were downregulated, alternative immune checkpoints for TIM-3, VISTA and CD276 (e.g., TIM-3, VISTA and CD276) were significantly upregulated. This suggests that cancer learns to escape treatment by switching to different molecular escape routes.
This finding could guide future therapeutic strategies. Doctors may not need an immune checkpoint, but rather a combined approach to blocking multiple escape routes at the same time.
Going towards a bigger experiment
Encouraging results prompted a larger Phase 3 clinical trial, which now recruits patients in 28 locations in the United States, Europe and Israel. The aim of this study was to recruit more than 740 patients, including patients with varying degrees of tumor levels in the resection surgery, by April 2029.
“Further research is needed to determine the best effect of surgery in this case, but these findings may bring hope, especially for patients with glioblastoma who do not have surgery.”
This study represents not only another combination of treatments. It demonstrates how understanding cancer biology at the molecular level can reveal unexpected treatment opportunities that translate what looks like a disadvantage (inoperative tumor) into a therapeutic advantage.
About 25% of patients with glioblastoma who cannot safely remove tumors provide something that was previously in short supply: hopefully based on rigorous science and a clear understanding of the cause of the treatment.
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